Novel Drug Ups Survival in Multiple Myeloma

by Ed Susman Contributing Writer, MedPage Today

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Pomalidomide, a novel immunomodulatory drug, in combination with low-dose dexamethasone, significantly improved overall survival compared with high-dose dexamethasone in patients in patients with multiple myeloma who were refractory to bortezomib and refractory to or otherwise ineligible for thalidomide or lenalidomide.

ATLANTA – Patients with relapsed or refractory multiple myeloma who were out of treatment options showed an increased disease-free progression and overall survival when treated with the investigational agent pomalidomide, researchers said here.

The combination of pomalidomide -- a derivative of thalidomide that is anti-angiogenic and acts as as imunomodulator -- and low-dose dexamethasone resulted in a median disease-free progression interval of 15.7 weeks, compared with 8 weeks (P<0.001) in patients treated with high-dose dexamethasone, said Meletios Dimopoulos, MD, professor and chairman of clinical therapeutics at Alexandria Hospital in Athens.

Overall survival was a median of 34 weeks with high-dose dexamethasone, but after more than 60 weeks of treatment the median overall survival for those on pomalidomide and low-dose dexamethasone had not been reached (P<0.001), Dimopoulos said at the annual meeting of the American Society of Hematology.

"We are excited about these results, as they show that a combination approach with pomalidomide and low-dose dexamethasone offers superior results than current treatment options for hard-to-treat myeloma patients," he said.

"Based on these data, pomalidomide plus low dose dexamethasone should become the new standard of care in patients who have exhausted the novel agents lenalidomide (Revlimid) and bortezomib (Velcade)," he said in a press briefing.

In the open-label, multicenter, phase III trial, Dimopoulos and colleagues enrolled 455 patients, assigning 302 patients to the pomalidomide arm of the study and 153 patients to the high-dose dexamethasone arm.

In the pomalidomide arm of the study, the experimental drug was delivered at a dose of 4 mg/day for Days 1-21 in a 28-day cycle. Patients took the treatment until disease progression or intolerable adverse events. They also were given a 40-mg dose of dexamethasone; patients over age 75 were given a 20-mg dose of dexamethasone. The steroid was given on Days 1, 8, 15 and 22 in the 28-day cycle.

In the high-dose dexamethasone-only study arm, patients received a dose of 40 mg of dexamethasone on Days 1-4, 9-12 and 17-20 in the 28-day cycle. Again, older patients received it at a lower dose.

After an independent review committee concluded that the combination regimen offered survival advantage, the study's Data Safety Monitoring Board recommended that patients from the dexamethasone monotherapy arm be switched to the pomalidomide arm.

Aaron Schimmer, MD, PhD, moderator of the press conference and a clinician scientist at the Princess Margaret Cancer Centre, University Health Network in Toronto, told MedPage Today, "For patients with very few options, this will be a useful drug."

"The next question is: How far up can you start to use this? Does it have efficacy in less heavily treated patients? Hopefully the answer is Yes and we can move it further up the treatment ladder," he said.

Dimopoulos noted that multiple myeloma causes abnormal plasma cells to accumulate in the bone marrow, interfering with normal blood cell production and increasing the risk of infection and abnormal bleeding. Current treatments include combinations of steroid therapies like dexamethasone, which reduces inflammation and manages the immune response with targeted therapies like bortezomib and lenalidomide that inhibit tumor growth and reproduction.

However, many patients eventually become resistant to these standard therapies and therefore have a poor prognosis.

Dimopoulos reported that the combination regimen was well tolerated among the study participants, although some expected toxicities were reported in both groups. The main reason for discontinuation was progressive disease, which occurred in 35% of patients in the pomalidomide arm and in 49% of the high-dose dexamethasone patients. About 25% of the patients in the combination group died during the study, compared with 38% on high-dose dexamethasone.

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